{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:56:30Z","timestamp":1791384990199,"version":"4.3.3"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Pancreatic ductal adenocarcinoma (PDAC) is among the most radioresistant malignancies. Proton therapy assumes a uniform relative biological effectiveness (RBE) of 1.1 regardless of radiation quality. We characterized proton RBE as a function of dose-mean lineal energy (\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      ) in PDAC cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Proton RBE was assessed in Panc-1 and COLO 357 FG cells using a high-throughput 96-well irradiation platform with an 81.4 MeV spot-scanning proton beam. Cells were irradiated at 12 discrete depths along the pristine Bragg curve, spanning\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      values of 1.9 to 20.0 keV\/\u03bcm. Dose was varied by adjusting spot-scanning repaintings. Parallel 6 MV photon irradiations (\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      = 0.8 keV\/\u03bcm) served as reference. Cell viability was assessed by crystal violet assay and fitted with the linear-quadratic (LQ) model to extract RBE at 10% viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both cell lines demonstrated RBE near 1.0 at entrance energies (\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      &amp;lt; 10 keV\/\u03bcm). Beyond the Bragg peak, RBE rose sharply: for Panc-1, RBE reached 3.0 \u00b1 0.3 at\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      = 18.7 keV\/\u03bcm and 4.6 \u00b1 0.4 at\n                      <jats:italic>\n                        \u0233\n                        <jats:sub>D<\/jats:sub>\n                      <\/jats:italic>\n                      = 20.0 keV\/\u03bcm; for COLO 357 FG, RBE reached 3.6 \u00b1 0.2 and 6.1 \u00b1 0.5 at the same positions. For Panc-1, LQ fits were good across all conditions. In contrast, COLO 357 FG exhibited a linear dose-response (\u03b2\u22480) for protons despite a clear LQ response to photons, suggesting proton-induced damage complexity exceeds the repair capacity of this cell line.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The clinical RBE = 1.1 assumption substantially underestimates proton effectiveness in the distal Bragg peak region for PDAC. This microdosimetric RBE dataset provides a quantitative basis for improving proton treatment planning in radioresistant PDAC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1934487","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:31:32Z","timestamp":1789533092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Microdosimetric characterization of proton relative biological effectiveness in pancreatic ductal adenocarcinoma cell lines"],"prefix":"10.3389","volume":"16","author":[{"given":"Tianyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]},{"name":"Cancer Biology Program, The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences","place":["Houston, TX, United 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